Biologic sealants comprising fibrinogen and thrombin are known. Cross-linked fibrin sealant is formed when fibrinogen and thrombin are mixed together but the formed fibrin sealant is subject to undergo enzymatic degradation with plasmin. Such sealants degrade and absorb in about 4 to 7 days, while the sealant mechanical strength and tissue bonding ability must be retained until the wound heals, which can take up to about 14 days. One method for controlling fibrin sealant enzymatic degradation has been to incorporate tranexamic acid or aprotinin into the tissue sealant formulation components. Other means have been explored for improving the strength of fibrin-based adhesive/sealants, such as incorporating collagen.
Fibrin hydrogels fall within a class of biomaterials that have great scaffolding potential in many tissue engineering applications due to their high tissue-like water content, high biocompatibility in general, mechanical properties that parallel the properties of soft tissues, efficient transport of nutrients and waste, powerful ability to uniformly encapsulate cells, and ability to be injected as a liquid that gels in situ. The fibrin hydrogel as a potential scaffold has low mechanical stiffness and rapid degradation before the proper formation of tissue engineered structures.
In order to improve the low mechanical stiffness for some tissue engineering applications, fibrin hydrogels can be combined with other scaffold materials such as gelatin, hyaluronic acid, chondroitin-6-sulfate, collagen and chitosan to obtain constructs with desired mechanical strength. To prolong degradation of fibrin glue several approaches have been taken, including introducing highly crosslinked Fibrin Micro Beads (FMBs) or removal of proteins that are believed to aid in degradation of fibrin clot for e.g. plasmin.
Published PCT Publication WO1999/066964 by Tammishetti et al. entitled “Carbodiimide crosslinked albumin for bioadhesives, surgical sealants, and implantable devices”, teaches a method for producing a cross-linked albumin composition for use in a bioadhesive, surgical sealant or implantable device, comprising the steps of: (a) providing an albumin preparation; (b) providing a carbodiimide preparation; and (c) mixing said albumin preparation and said carbodiimide preparation under conditions which permit cross-linking of said albumin.
U.S. Pat. No. 6,371,975 by Cruise et al. entitled “Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers” discloses a biocompatible and biodegradable barrier material that can be applied to a tissue region, e.g., to seal a vascular puncture site. The barrier material comprises a compound, which is chemically cross-linked without use of an enzyme to form a non-liquid mechanical matrix. The compound preferably includes a protein comprising recombinant or natural serum albumin that is mixed with a polyethylene glycol (PEG)-derived polymer, and, most preferably, a multi-armed PEG polymer.
U.S. Pat. No. 6,833,408 by Sehl, et al. teaches a method of repairing damaged tissue in a patient comprising the steps of: placing into contact with the damaged tissue an adhesive composition comprised of (i) a hydrophilic polymer; (ii) a crosslinkable component having several nucleophilic groups; and (iii) a crosslinkable component having several electrophilic groups capable of reaction with the nucleophilic groups to form covalent bonds, wherein crosslinkable components are biocompatible and nonimmunogenic, and at least one of components is hydrophilic polymer. Cross-linking of the composition is said to result in a biocompatible, nonimmunogenic, cross-linked matrix.
U.S. Pat. No. 7,868,123 entitled “Derivatized tertiary amines and uses thereof” teaches tertiary amine intermediate and electrophilic monomers derived therefrom. The invention also relates to adhesives or sealants derived from such electrophilic moieties.
Published U.S. Patent Application No. 2008/0220047 by Sawhney et al. and entitled “Low-swelling biocompatible hydrogels” teaches surgical treatment for treating a tissue inside a vertebral column by forming a low-swelling biodegradable hydrogel in situ that is adherent to a tissue inside the vertebral column. Sawhney teaches a method comprising: forming a low-swelling biodegradable hydrogel by in situ polymerization that is adherent to tissue inside a vertebral column and substantially exterior to the vertebral column, wherein the first functional groups comprise nucleophiles and the second functional groups comprise electrophiles, wherein the first synthetic precursor is selected from the group consisting of dilysines, trilysines, and tetralysines, wherein the second synthetic precursor comprises a multi-armed precursor possessing a core and arms, the arms each comprising a polyethylene glycol having a molecular weight from about 250 to about 5000, wherein the core is selected from the group consisting of polyethers, polyamino acids, proteins, and polyols, and wherein forming the hydrogel comprises reacting a first synthetic precursor comprising at least three of a first functional group with a second synthetic polymer precursor comprising at least three arms that each comprise a second functional group, wherein the first functional group reacts with the second functional group to form covalent crosslinks between the first synthetic precursor and the second synthetic polymer precursor, and wherein the hydrogel swells upon exposure to a physiological solution.
Published U.S. Patent Application No. 2007/0280988 by Ludwig et al. and entitled “Coating layers for medical devices and methods of making the same” teaches methods for controlling the morphology and the release-rate of active agent from coating layers for medical devices comprising a polymer matrix and one or more active agents. The methods comprise fixing the morphology or phase distribution of the active agent prior to removing solvent from the coating composition. The coating layers can be used for controlled delivery of an active agent or a combination of active agents.
Published U.S. Patent Application No. 2010/0173843 by Hnojewyj and entitled “Tissue Adhering Compositions” discloses a method which mixes a first component, a second component, and a buffer material. The first component includes an electrophilic polymer material comprising poly(ethylene glycol) having a functionality of at least three. The second component includes a nucleophilic material comprising a natural or synthetic protein at a concentration of about 25% or less that, when mixed with the first component within a reaction pH range, cross-links with the first component to form a non-liquid, three-dimensional barrier. The buffer material includes tris-hydroxymethylaminomethane having a pH within the reaction pH range. The method applies the mixture to adhere to a tissue region.
Published U.S. Patent Application No. 2010/0063459 A1 discloses an adhesive material for medical use comprising gelatin and a non-toxic cross-linking material, such as transglutaminase. An optional embodiment of the invention includes dressings in which a layer of a transglutaminase is sandwiched between a first and second layer of gelatin. The hemostatic products are useful for the treatment of wounded tissue.
U.S. Pat. No. 6,730,299 is directed to an adhesive protein foam for surgical and/or therapeutic uses discloses an adhesive matrix that is produced using a mixture of a protein compound in solution, preferably of the native collagen, of the heated collagen or of the albumin, with an oxidized polysaccharide or mucopolysaccharide, preferably oxidized starch, oxidized dextran or oxidized hyaluronic acid.
Published Patent Application No. WO1998/000161 A1 entitled “Fibrin-based systems for controlled release of medicinal” discloses a medicinal delivery system based on the enzyme-catalyzed conversion of fibrinogen to fibrin that forms a gel to entrap the medicinal. For certain protein medicinals, after adequate fibrinogen conversion but prior to gelation, a thrombin inhibitor is added along with the medicinal protein to protect the medicinal protein from fragmentation by the action of thrombin. The erosion rate of the matrix is altered by incorporation of fibrinolysis inhibitors, adjusting the concentration of matrix components, and including Factor XIII at various levels.
Published U.S. Patent Application No. 2009/0010982 A1 entitled “Biocompatible adherent sheet for tissue sealing” discloses a biocompatible adherent sheet for use in surgical and medical procedures for sealing the tissues of a living mammal, preferably a human. The biocompatible adherent sheet includes a carrier sheet including a biocompatible polymer and a modified chitosan evenly disposed on one or both surfaces of the carrier sheet. Methods of preparing a biocompatible adherent sheet and methods of using a biocompatible adherent sheet are also provided. The biocompatible adherent sheet may also include a bioactive agent and other active ingredients. The biocompatible adherent sheet is a soft, pliable material that adheres to various tissues, bends easily around curved surfaces, and can withstand moderate burst pressures. Further, the biocompatible adherent sheet described therein is said to provide better adhesion to body tissues than existing materials.
U.S. Pat. No. 6,132,759 entitled “Medicaments containing gelatin cross-linked with oxidized polysaccharides” discloses a wound dressing comprising a biopolymer matrix comprising gelatin cross-linked with an oxidized polysaccharide. Preferably said oxidized polysaccharide comprises an oxidized dextran or an oxidized xanthan. Preferably said matrix is in the form of a hydrated film, a hydrated or dry foam, dry fibers which may be fabricated into a woven or non-woven tissue, hydrated or dry microbeads, dry powder; or said matrix is covered with a semipermeable film, so as to control the humidity of the wound covered with the dressing, with the permeability chosen so as to maintain this humidity within a therapeutically optimal window. A polysulfated polysaccharide with a M.W. greater than 30,000 kDa is mechanically entrapped during the formation of said matrix.
Published U.S. Patent Application No. 2006/0078536 A1 entitled “Polysaccharide-based polymer tissue adhesive for medical use” discloses a kit comprising: a) a first aqueous solution comprising an oxidized polysaccharide containing aldehyde groups, having a molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 5% to about 40% by weight of the oxidized polysaccharide; and b) a second aqueous solution comprising a water-dispersible, multi-arm polyether amine wherein at least three of the arms are terminated by a primary amine group, wherein the multi-arm polyether amine has a molecular weight of about 450 to about 200,000 Daltons, said solution containing from about 5% to about 70% by weight of the multi-arm polyether amine.
Published U.S. Patent Application No. 2005/0002893 A1 entitled “Composition consisting of a polymer containing amino groups and an aldehyde containing at least three aldehyde groups” discloses a composition of at least two biocompatible components that can be chemically crosslinked together, in particular for gluing biological tissue, comprising at least the following components: a) aqueous solution of at least one polymer having amino groups b) aqueous solution of at least one aldehyde having at least three aldehyde groups, where the composition is free of protein. The invention further relates to a provision of the composition for use as surgical tissue glue, and to a kit consisting of two substantially separate containers which contain components of the composition.
U.S. Pat. No. 6,096,309 entitled “Compositions containing thrombin and microfibrillar nanometer collagen, and methods for preparation and use thereof” discloses thrombin-containing hemostatic compositions, their preparation and use. In particular, the patent relates to hemostatic compositions comprising stabilized thrombin and microfibrillar collagen in an aqueous medium. The compositions are used in a kit comprising two different components, one of which is autologous patient's plasma as the source of fibrinogen, and the other of which is the thrombin-containing composition which also contains microfibrillar collagen having an average diameter of about 3-30 nanometers.
Other background references, include patent publications EP2,100,628 A1 “Self-degradable adhesive for medical use of two-component reactant system comprising powder-liquid or powder-powder”; published PCT application WO2008/005207 A2 entitled “Tissue adhesives with modified elasticity”; published US Patent Application No. 2008/0319101 A1 entitled “Medical-use two part reactive adhesive and medical-use resin having self-degradation property”; published US Patent Application No. 2008/0213243 A1 entitled “Hemostatic materials and dressing”; published US Patent Application No. 2008/0075657 A1 entitled “Biopolymer system for tissue sealing”; and published US Patent Application No. 2003/0232746 A1 entitled “Cross-linked bioactive hydrogel matrices”.
Additional related background references include publications: Catheterization and Cardiovascular Diagnosis 41:79-84 (1997) that discloses collagen as a reinforcement matrix in fibrin sealant; “Fibrin: A versatile Scaffold for Tissue Engineering Applications”, Tissue Engineering: Part B Volume 14, Number 2, 2008, pgs. 199-215; and “Cross-linking of human fibrinogen with glutaraldehyde and tetranitromethane”, Thrombosis research (1975), 7, 827-38.